1. Toxicity evaluation of the photoprotective compound LQFM048: Eye irritation, skin toxicity and genotoxic endpoints.
- Author
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de Ávila RI, de Sousa Vieira M, Gaeti MP, Moreira LC, de Brito Rodrigues L, de Oliveira GA, Batista AC, Vinhal DC, Menegatti R, and Valadares MC
- Subjects
- 3T3 Cells, Animals, Cattle, Cell Line, Transformed, Cell Survival drug effects, Cell Survival physiology, Cell Survival radiation effects, Chickens, Cornea physiology, Cornea radiation effects, Dose-Response Relationship, Drug, Drug Evaluation, Preclinical methods, Female, Hep G2 Cells, Humans, Irritants administration & dosage, Mice, Mice, Inbred BALB C, Mutagenicity Tests methods, Random Allocation, Skin metabolism, Skin radiation effects, Ultraviolet Rays adverse effects, Cornea drug effects, Irritants toxicity, Skin drug effects, Sunscreening Agents toxicity
- Abstract
A new molecule, LQFM048, originally designed through molecular hybridization using green chemistry approach, is in development as a photoprotective agent. Eye irritation, skin toxicity and genotoxicity evaluations are mandatory for predicting health risks. In this context, the purpose of this study was to investigate the eye irritation potential of LQFM048 by combining Short Time Exposure (STE), Bovine Corneal Opacity and Permeability (BCOP) associated with corneal histomorphometry and Hen's Egg Test-Chorioallantoic Membrane (HET-CAM). Additionally, skin toxicity was evaluated by interleukin-18 production in the HaCaT keratinocyte, Local Lymph Node Assay (LLNA:BrdU-ELISA) method, 3T3 Neutral red uptake (NRU) assay and in vivo phototoxicity test. Genotoxic potential of LQFM048 was also analyzed by cytokinesis-block micronucleus assay (MNvit test-cytoB) in HepG2 cells. Our results showed that LQFM048 did not induce eye irritation and it was classified as UN GHS No Category for both STE and BCOP assays and non-irritating for HET-CAM test. LQFM048 showed non-potential skin sensitization with stimulation index (SI=0.7) in the LLNA:BrdU-ELISA method. Corroborating in vivo tests, it did not promote significant cytotoxicity in HaCaT cells and it showed similar levels of IL-18 when compared to control. Furthermore, LQFM048 induced non-phototoxic potential with photo-irritation factor (PIF) and mean photo effect (MPE) of 1 and -0.138, respectively, for 3T3 cells. Similarly, it was not phototoxic for in vivo testing with or without exposure to UVA, showing SI values of 1 and 1.2, respectively. The micronucleus test showed that LQFM048 was not genotoxic, under the conditions tested.In conclusion, LQFM048, a heterocyclic compound obtained through an environmentally acceptable simple synthetic route, seems to be safe for human use, especially for the development of a new sunscreen product, since it is neither an eye irritant, nor a contact allergen, nor mutagenic and nor phototoxic., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2017
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